Small molecules, enormous functions: potential approach for overcoming bottlenecks in embryogenic tissue induction and maintenance in conifers.

Somatic embryogenesis (SE) is not only the most effective method among various strategies for the asexual propagation of forest trees but also a basis for genetic improvement. However, some bottlenecks, such as the recalcitrance of initiation, the maintenance of embryogenic potential during proliferation and the low efficiency of maturation as well as high rate of abnormal embryo development remain unresolved. These bottlenecks refer to complex mechanisms, including transcriptional regulatory networks, epigenetic modifications and physiological conditions. In recent years, several small molecules utilized in animal stem cell research have exhibited positive effects on plant regeneration, including conifer species, which offers a potential novel approach to overcome the challenges associated with SE in conifers. In this review, we summarize the small molecules used in conifers, including redox substances, epigenetic regulatory inhibitors and other metabolism-related molecules, which overcome these difficulties without the use of genetic engineering. Moreover, this approach also has the advantages of dynamic reversibility, simple operation, and simultaneous regulation of multiple targets, which might be one of the best choices for optimizing plant regeneration systems including SE.

The effect of ocrelizumab on Balo's tumefactive lesion: A case report.

Balo's concentric sclerosis (BCS) is a rare subtype of multiple sclerosis. Advanced MRI metrics, such as magnetization transfer ratio (MTR), fractional anisotropy (FA), mean diffusivity (MD), and the ratio of total N-acetylaspartate concentration/total creatine concentration (tNAA/tCr) using proton magnetic resonance spectroscopy (1H-MRS), are commonly used in research studies to investigate the effect of a disease modifying therapy (DMT). We report a patient diagnosed with BCS, receiving ocrelizumab, and provide a comparison of the lesion volume, T1-gadolinium lesion volume, MTR, FA, MD, and MRS metrics at baseline, 6- and 12-month follow-up. There was a reduction in Balo's lesion volume on fluid-attenuated inversion recovery (FLAIR) imaging observed in our patient from baseline (23.925 mL) to 12-month follow-up (2.391 mL), with the largest decrease from baseline to 6-month follow-up (3.650 mL). There was no T1-gadolinium enhancement seen at month 6 and 12. The MTR of the lesion did not change significantly (baseline = 50.9%, 6-month = 49.9%, 12-month =50.1%) but the FA increased from 0.188 (at baseline) to 0.304 (at 6 months), while the 12-month follow-up FA was 0.297. We also noted a reduction in MD from baseline (1.333 × 10-3 mm2/s) to 6-month follow-up (1.037 × 10-3 mm2/s), while the 12-month follow-up MD was 1.086 × 10-3 mm2/s. There was a 10.3% increase in tNAA/tCr from 1.583 (at month 0) to 1.747 (at month 12). Our results demonstrate for the first time a direct effect of ocrelizumab on BCS lesions. To validate our findings, more observations are needed in a larger group of BCS patients.

Choroid plexus volume as a marker of retinal atrophy in relapsing remitting multiple sclerosis.

OBJECTIVE: To evaluate choroid plexus (CP) volume as a biomarker for predicting clinical disability and retinal layer atrophy in relapsing remitting multiple sclerosis (RRMS). METHODS: Ninety-five RRMS patients and 26 healthy controls (HCs) underwent 3 T whole brain MRI, expanded disability status scale (EDSS) and optical coherence tomography (OCT). Fully automated intra-retinal segmentation was performed to obtain the volumes of the retinal nerve fiber layer (RNFL), combined ganglion cell layer -inner plexiform layer (GCIPL), inner nuclear layer (INL), outer plexiform layer (OPL), outer nuclear layer (ONL), retinal pigment epithelium (RPE), total macular volume (TMV) and papillomacular bundle (PMB). Automated segmentation of the CP within the lateral ventricles was performed and the choroid plexus volume (CPV) was normalized by total intracranial volume (TIV). Linear regression analysis and generalized estimating equation (GEE) models were applied to evaluate relationships between nCPV and EDSS, T2 lesion volume, disease duration, and retinal layer volumes, followed by Bonferroni correction analysis for multiple comparisons. RESULTS: RRMS patients had larger tChPV compared to HCs (p < 0.001). After Bonferroni correction, there was a significant positive correlation between tChPV and EDSS (r2 = 0.25, p = 0.0002), disease duration (r2 = 0.30, p = 0.01), and T2 lesion volume (r2 = 0.39, p = 0.0000). A robust negative correlation was found between tChPV and RNFL (p < 0.001), GCIPL (p = 0.003), TMV (p = 0.0185), PMB (p < 0.0001), G (p = 0.04), T(p = 0.0001). CONCLUSIONS: Our findings support the association of tChPV with disability and altered retinal integrity in RRMS.

Role of white matter in cognitive impairment among relapsing remitting multiple sclerosis patients.

BACKGROUND: Multiple Sclerosis (MS) associated cognitive impairment is believed to be mostly connected with damage to gray matter. The contribution of white matter is still poorly understood. We aim to examine the relationship between cognition and white matter tracts among relapsing remitting MS (RRMS) patients. METHODS: Thirty RRMS patients were selected undergo the (3-seconds-interstimulus-interval paced auditory serial addition test) PASAT-3, the (symbol digit modalities test (SDMT) and full-brain MRI scans on a SIEMENS 3 Tesla Verio scanner. Diffusion Tensor Imaging (DTI) parameters, such as fractional anisotropy (FA) and mean diffusivity (MD) were examined in 37 white matter (WM) tracts. WM tracts were selected from the association pathways, projection pathways, commissural pathways by applying Human Connectome project (HCP)842 tractography atlas after DTI data reconstruction and registration to HCP1065 diffusion template in DSI Studio (version March 2021) In SPSS v26, Spearman's rank correlation analysis was used to examine the connection between DTI WM tracts and cognitive scores. The power of the study was increased by using false discovery rate (FDR) software. RESULTS: The mean scores on the PASAT-3 and SDMT were 31.5 ± 12.8 and 46.9 ± 16.7 respectively. Better cognitive performance was correlated to higher FA values, while lower cognitive function was correlated to higher MD values. There was a positive correlation between FA values in the right medial lemniscus and superior cerebellar peduncle and SDMT scores (p 0.05). Additionally, there was a trend for significance between the FA values in the left corticothalamic tract and SDMT scores. MD values in the superior cerebellar peduncle, left arcuate Fasciculus and left extreme capsule were negatively correlated with SDMT scores (p<0.05). PASAT-3 scores were negatively correlated with MD values in the right cerebellum, however, there was no significant correlation between PASAT-3 and FA values. CONCLUSIONS: White matter tracts, particularly the superior cerebellar peduncle, contribute to the cognitive impairment in RRMS. Larger sample sizes for longitudinal research are necessary.

Impact of Disease Modifying Therapy on MS-Related Fatigue: A Narrative Review.

Multiple sclerosis (MS) is a chronic autoimmune disease that affects the central nervous system by causing inflammation, demyelination and neurodegeneration. Fatigue is the most prevalent and one of the most disabling symptoms among people with MS (pwMS). Due to its complexity and subjective character, fatigue is still little understood despite its frequent occurrence and severe impact. The potential causes, effects, and treatments of fatigue associated with MS have been extensively studied in recent years. Though the benefits of such a variety of contributions are obvious, there have not been many attempts to evaluate the effect of disease modifying therapies (DMTs) on MS-related fatigue. In this review, we summarize clinical trials and research studies, and we discuss the effect of different DMTs on MS-related fatigue.

Effect of Obesity on Retinal Integrity in African Americans and Caucasian Americans With Relapsing Multiple Sclerosis.

Objective: To study the effect of obesity on retinal structures in African Americans (AAs) and Caucasian Americans (CAs) with relapsing-remitting multiple sclerosis (RRMS). Methodology: About 136 patients with RRMS without history of optic neuritis were divided into two groups, based on body mass index (BMI): 67 obese (40 AA, 27 CA, mean BMI ± SD: 36.7 ± 5.8), and 69 non-obese (23 AA, 46 CA, mean BMI ± SD: 24.0 ± 3.1). The peripapillary retinal nerve fiber layer (pRNFL) thickness was quantified by optical coherence tomography (OCT) and was segmented into quadrant thickness: superior (S), inferior (I), temporal (T), and nasal (N). Papillomacular bundle (PMB) thickness, retinal nerve fiber layer (RNFL), ganglion cell + inner plexiform layer (GCIPL), inner nuclear (INL), outer plexiform (OPL), outer nuclear (ONL), and total macular (TMV) volumes were obtained. Results: Obesity was associated with lower T thickness (58.54 ± 15.2 vs. 61.9 12.4, p = 0.044), higher INL (0.98 ± 0.07 vs. 0.96 ± 0.06, p = 0.034), and lower RNFL (0.77 ± 0.14 vs. 0.82 ± 0.12, p = 0.009) volumes. Obese AA had significantly thinner T (58.54 ± 15.19 vs. 61.91 ± 12.39, p = 0.033), N (68.94 ± 2.7 vs. 77.94 ± 3.3, p = 0.044), and TMV (8.15 ± 0.07 vs. 8.52 ± 0.09, p = 0.003), RNFL (0.74 ± 0.02 vs. 0.82 ± 0.02, p = 0.013), OPL (0.76 ± 0.01 vs. 0.79 ± 0.1, p = 0.050), ONL (1.68 ± 0.031 vs. 1.79 ± 0.038, p = 0.026), and GCIPL (1.78 ± 0.04 vs. 1.9 ± 0.05, p = 0.038) compared to obese CA. Among patients with non-obesity, the ONL was significantly lower in AA (1.78 ± 0.04 vs. 1.9 ± 0.05, p < 0.001). Conclusions: Obesity is associated with retinal structure abnormalities in patients with RRMS. Its impact might be more prominent in AA than CA. Large longitudinal studies are needed to validate our findings.

Cortical surface thickness, subcortical volumes and disability between races in relapsing-remitting multiple sclerosis.

BACKGROUND: The interplay between cortical surface thickness (CTh), subcortical volumes (SCV) and disability in patients with relapsing remitting multiple sclerosis (RRMS) is still not clear. OBJECTIVE: To examine the relationship between CTh, SCV, and disability and investigate differences in CTh, SCV and disability between African Americans (AA) and Caucasian Americans (CA). METHODS: Sixty-five RRMS (33AA, 32 CA) participants underwent Expanded Disability Status Scale and Multiple Sclerosis Functional Composite (MSFC) assessments, including timed 25-foot walk (T25FW), nine-hole peg test (9HPT) on dominant (D) and non-dominant hand (ND) and paced auditory serial addition test (PASAT-3). Symbol digit modalities test (SDMT) was also administered. All participants underwent 3T brain MRI. CTh was measured in the Frontal (FA), Parietal (PA), Temporal (TA), Occipital (OA), Cingulate (CA), and Global (GA) cortical surface areas (CSA). SCV measurements included Thalamus (TV), Caudate (CV), Putamen (PV), Pallidum (PaV), Hippocampus (HV), Amygdala (AV), Accumbens (AcV), Brain Stem (BSV), and Deep Gray Matter Total Volume (DGMTV). A general linear model with multivariate analysis (MANOVA) was used to determine the differences between the two cohorts (SPSS vs 25). Spearman rank correlation analysis was performed to investigate the relationship between CTh and MSFC. RESULTS: AA have significantly decreased FA, PA, TA, GA CTh compared to CA (p = 0.004, p = 0.018, p = 0.013, p = 0.015, respectively). SCV measurements were not significantly different. Only in CA, the MSFC measures correlate significantly with regional CSA CTh. In both races and in the entire group, T25FW correlates with TV, PV, AV, AcV and DGMTV (p < 0.05). Only in AA and the entire cohort, PASAT-3 correlates with TV and AcV(p = 0.041, p = 0.006, p = 0.006, p = 0.000 respectively). CONCLUSIONS: Differences in CSA CTh reinforce the different disease pathobiology between AA and CA. Regional CTh may represent a useful biomarker related to multi-domain disability only in CA, while in AA DGM injury might be a more important contributor to disability. Longitudinal, large-scale studies are warranted to confirm our findings.

Multimodal MRI Response to Fingolimod in Multiple Sclerosis: A Nonrandomized, Single Arm, Observational Study.

BACKGROUND AND PURPOSE: Fingolimod has a favorable effect on conventional MRI measures; however, its neuroprotective effect is not clear. We aim to investigate changes of conventional and advanced MRI measures in lesions and normal-appearing white matter (NAWM) over 2 years in fingolimod-treated patients. METHODS: Fifty relapsing-remitting multiple sclerosis patients and 27 healthy controls were enrolled in the study and underwent baseline, 1-year, and 2-year 3T MRI scans. T2 lesion volume, whole brain volume, cortical gray matter volume, white matter volume, corpus callosum area, percentage brain volume change (PBVC), Expanded Disability Status Scale, gadolinium-enhancing lesions, PBVC, magnetization transfer ratio (MTR), and diffusion tensor imaging metrics (fractional anisotropy [FA] and median diffusivity [MD]) in lesions and NAWM were calculated. Longitudinal changes were examined using one-way repeated measures ANOVA. Bonferroni correction for multiple testing was used when appropriate. RESULTS: Conventional MRI measures were unchanged in both groups. Lesion MTR increased significantly (P < .001), but NAWM-MTR remained unchanged. Lesion FA improved significantly in year 1 (P = .003) and over the study duration (P = .05). Lesion MD changed significantly from baseline to year 1 (P < .001) and remained stable over 2 years. NAWM-FA was significant from baseline to year 1 (P = .002) and from baseline to year 2 (P < .001). NAWM-MD was significant only from baseline to year 1 (P = .001). CONCLUSIONS: These findings suggest a possible neuroreparative effect of fingolimod on the MS lesions and NAWM. Larger and longer randomized studies are required to confirm these results.

White and Gray Matter Abnormalities in Manifest Huntington's Disease: Cross-Sectional and Longitudinal Analysis.

BACKGROUND AND PURPOSE: Early white matter (WM) changes and cortical atrophy in Huntington's disease (HD) are often evident before disease onset and extend through the brain during manifest stages. The trajectory of these brain abnormalities in symptomatic stages remains relatively unexplored. The aim of this study is to investigate how the pattern of WM and gray matter (GM) alterations progress over time. METHODS: We investigated alterations in brain WM, cortical thickness, and subcortical structures using diffusion and structural magnetic resonance imaging, in manifest HD patients (n = 13) compared to age-matched healthy controls (n = 11). Imaging and clinical data for the HD group were collected at follow-up (7 months) to explore possible longitudinal changes. RESULTS: Cross-sectional analyses identified significant posterior cortical thinning (P < .05) and symmetric fractional anisotropy (FA) reduction (P < .01) in brain WM of HD group compared to HC. These changes were strongly correlated with impairment in motor symptoms and processing speed. Subcortical atrophy was significant in caudate, putamen, globus pallidus, and thalamus (P < .001). Regions of interest analysis revealed a significant reduction in FA of the corpus callosum (CC) (-2.19%, P < .05) upon follow-up, whereas no significant cortical thinning and subcortical atrophy was found. CONCLUSIONS: This study showed broad GM and WM abnormalities in manifest HD patients. Reductions in FA and cortical thinning correlated significantly with the disturbances of motor and cognitive processing that describe HD. Follow-up assessment showed that the CC is compromised in the absence of detectable GM changes or motor decline, suggesting it plays an important role in disease progression.

Characterizing Fatigue-Related White Matter Changes in MS: A Proton Magnetic Resonance Spectroscopy Study.

Few cross-sectional studies have investigated the correlation between neurochemical changes and multiple sclerosis (MS) fatigue, but little is known on the fatigue-related white matter differences between time points. We aim to investigate the longitudinal neurometabolite profile of white matter in MS fatigue. Forty-eight relapsing remitting multiple sclerosis (RRMS) patients with an expanded disability status scale (EDSS) ≤ 4 underwent high field 1H-multivoxel magnetic resonance spectroscopy (MRS) at baseline and year 1. Fatigue severity was evaluated by the fatigue severity scale (FSS). Patients were divided into low (LF, FSS ≤ 3), moderate (MF, FSS = 3.1-5), and high fatigue (HF, FSS ≥ 5.1) groups. In a two-way analysis of variance (ANOVA), we observed a decline in the ratio of the sum of N-acetylaspartate (NAA) and N-acetylaspartylglutamate (NAAG) to the sum of creatine (Cr) and phosphocreatine (PCr) in the right anterior quadrant (RAQ) and left anterior quadrant (LAQ) of the MRS grid in the HF group at baseline and year 1. This decline was significant when compared with the LF group (p = 0.018 and 0.020). In a one-way ANOVA, the fatigue group effect was significant and the ratio difference in the right posterior quadrant (RPQ) and left posterior quadrant (LPQ) of the HF group was also significant (p = 0.012 and 0.04). Neurochemical changes in the bilateral frontal white matter and possibly parietooccipital areas were noted in the HF group at two different time points. Our findings may shed some light on the pathology of MS fatigue.

Racial differences in retinal neurodegeneration as a surrogate marker for cortical atrophy in multiple sclerosis.

BACKGROUND: Multiple sclerosis (MS) has both an inflammatory and a neurodegenerative component, with gray matter (GM) atrophy being an important contributor to disability. Optical coherence tomography (OCT) may serve as a prognostic tool for neuroaxonal health by measuring ganglion cell inner plexiform layer (GCIPL) thickness. There is a paucity of literature regarding the effects of race on pathobiology of MS, as racial minorities are underrepresented in research studies. OBJECTIVE: The aim of this paper is to compare the correlation between GM fraction (GMF) and GCIPL thickness in Caucasian Americans with MS (CAMS) and African Americans with MS (AAMS). METHODS: Fifty-nine patients with relapsing-remitting multiple sclerosis (RRMS) were included. Using a cross-sectional design, we compared the OCT (GCIPL thickness) and MRI (GMF) data of 32 CAMS and 27 AAMS patients. RESULTS: No significant correlation was observed between GMF and GCIPL in our study group (p = 0.127, r = 0.148). CAMS exhibited a significant correlation between these measures (p = 0.0004, r = 0.434), while in AAMS these measures did not correlate significantly (p = 0.187, r = -0.201). CONCLUSION: GCIPL might be a sensitive biomarker predicting GM atrophy and disability in CAMS, but not in AAMS. Larger studies are needed to investigate reliable biomarkers across races. Inclusion of AAMS in research studies is necessary to shed more light on the pathobiology of MS.

Long-term safety of rituximab induced peripheral B-cell depletion in autoimmune neurological diseases.

BACKGROUND: B-cells play a pivotal role in several autoimmune diseases, including patients with immune-mediated neurological disorders (PIMND), such as neuromyelitis optica (NMO), multiple sclerosis (MS), and myasthenia gravis (MG). Targeting B-cells has been an effective approach in ameliorating both central and peripheral autoimmune diseases. However, there is a paucity of literature on the safety of continuous B-cell depletion over a long period of time. OBJECTIVE: The aim of this study was to examine the long-term safety, incidence of infections, and malignancies in subjects receiving continuous therapy with a B-cell depleting agent rituximab over at least 3 years or longer. METHODS: This was a retrospective study involving PIMND who received continuous cycles of rituximab infusions every 6 to 9 months for up to 7 years. The incidence of infection related adverse events (AE), serious adverse events (SAE), and malignancies were observed. RESULTS: There were a total of 32 AE and 4 SAE with rituximab treatment. The 3 SAE were noted after 9 cycles (48 months) and 1 SAE was observed after 11 cycles (60 months) of rituximab. There were no cases of Progressive multifocal leukoencephalopathy (PML) and malignancies observed throughout the treatment period. Rituximab was well tolerated without any serious infusion reactions. Also, rituximab was found to be beneficial in treating PIMND over a 7-year period. CONCLUSIONS: This study demonstrates that long-term depletion of peripheral B-cells appears safe and efficacious in treating PIMND. Longer and larger prospective studies with rituximab are needed to carefully ascertain risks associated with chronic B-cell depletion, including malignancies. Recognizing that this is a small, retrospective study, such data nonetheless complement the growing literature documenting the safety and tolerability of B-cell depleting agents in neurological diseases.

Effect of ginsenoside Rg1 on senescence characteristics of leukemic stem cells / 局解手术学杂志

Objective To explore the effect of ginsenoside Rg1 on leukemia stem cells through comparing the biological senescence characteristics of HSCs in the patients with leukemia and healthy people,and provide new ideas and methods for leukemia prevention and treatment.Methods Fifteen cases of normal bone marrow in normal group and sixteen cases of chronic myeloid leukemia in leukemia group were divided into control group and Rg1 group,respectively.The control group used the conventional culture.The Rg1 group used the culture system with 10 μg/mL ginsenoside Rg1,other conditions were the same as control group.The bone marrow mononuclear cell of all groups were extracted after 2 days,and the CD34 +/CD38-cells population was isolated and purified by immunomagnetic adsorption cell sorting(MACS).The purity of the cells and cell cycles phase were detected by flow cytometry.Cell viability was detected by trypan blue staining.The percentage of positive cells was detected by SA-β-gal staining.CCK-8 detected the CD34 +/CD38-proliferation ability of each group.Results The ratio of CD34 +/CD38-cell population was (1.76 ± 0.34) ％ in every 1 × 106 BMNCs before sorting;the proportion of CD34 +/CD38-cell population per 1 × 106 cells after immunomagnetic sorting was (91.15 ± 2.41)％.The positive rate of SA-β-gal staining in human bone marrow CD34 +/CD38-cells of leukemia Rg1 group was significantly higher than that in leukemia control group,the difference was not significant (P ＞ 0.05);meanwhile there was no significant difference between normal control group and normal Rg1 group,but higher than that in leukemia control group,the difference was significant(P ＜ 0.05).CCK-8 results showed that the proliferation of CD34 +/CD38-cells was significantly increased in leukemia control group than those in the other groups.The survival rate of CD34 +/CD38-cells in human bone marrow was 99.1％ in all groups.Cell cycle phase results showed that the G1 arrest of CD34 +/CD38-cells in leukemia control group was significantly lower than those in the other three groups.Conclusion CD34 +/CD38-cells in chronic myeloid leukemia patients may be caused by some chronic myeloid leukemia.Ginsenoside Rg1 can effectively delay the process of aging.

Structural and Neuronal Integrity Measures of Fatigue Severity in Multiple Sclerosis.

Fatigue is a common and disabling symptom in Multiple Sclerosis (MS). However, consistent neuroimaging correlates of its severity are not fully elucidated. In this article, we study the neuronal correlates of fatigue severity in MS. Forty-three Relapsing Remitting MS (RRMS) patients with MS-related fatigue (Fatigue Severity Scale (FSS) range: 1-7) and Expanded Disability Status Scale (EDSS) ≤ 4, were divided into high fatigue (HF, FSS ≥ 5.1) and low fatigue groups (LF, FSS ≤ 3). We measured T2 lesion load using a semi-automated technique. Cortical thickness, volume of sub-cortical nuclei, and brainstem structures were measured using Freesurfer. Cortical Diffusion Tensor Imaging (DTI) parameters were extracted using a cross modality technique. A correlation analysis was performed between FSS, volumetric, and DTI indices across all patients. HF patients showed significantly lower volume of thalamus, (p = 0.02), pallidum (p = 0.01), and superior cerebellar peduncle ((SCP), p = 0.002). The inverse correlation between the FSS score and the above volumes was significant in the total study population. In the right temporal cortex (RTC), the Radial Diffusivity ((RD), p = 0.01) and Fractional Anisotropy ((FA), p = 0.01) was significantly higher and lower, respectively, in the HF group. After Bonferroni correction, thalamic volume, FA-RTC, and RD-RTC remained statistically significant. Multivariate regression analysis identified FA-RTC as the best predictor of fatigue severity. Our data suggest an association between fatigue severity and volumetric changes of thalamus, pallidum, and SCP. Early neuronal injury in the RTC is implicated in the pathogenesis of MS-related fatigue.

Cerebrospinal fluid humoral immunity in the differential diagnosis of multiple sclerosis.

BACKGROUND: The diagnostic accuracy of cerebrospinal fluid oligoclonal bands (CSF-OCB) detected by isoelectric focusing (IEF) in patients with multiple sclerosis (MS) was evaluated in our study. METHODS: Three hundred and twenty-one patients with MS and other central nervous system (CNS) immune mediated disorders were assessed (CIMD). Cerebrospinal fluid and matched serum samples were examined for the presence of OCB by IEF-IB (isoelectric focusing with immunoblotting). RESULTS: Isolated oligoclonal bands (ISO-OCB) were the only predictor of MS diagnosis independent of age, gender and CSF-OCB. ISO-OCB ≥ 3.5 detected by IEF yielded a sensitivity of 98% and specificity of 87% in distinguishing MS from MS mimickers. CONCLUSIONS: For the neurologist, a score of ≥ 4 ISO-OCB supports the diagnosis of MS. On the other hand, ISO-OCB ≤3 favors CIMD. Further studies with larger population samples are warranted to confirm these findings.

Cerebral Gray Matter Atrophy Is Associated with the CSF IgG index in African American with Multiple Sclerosis.

BACKGROUND AND PURPOSE: African American (AA) patients with multiple sclerosis (MS) have been reported to have a more aggressive disease course compared to their white counterparts. We explored the relation of gray matter (GM) volume, a marker of tissue injury, and cerebrospinal fluid (CSF) IgG index in both AA and white MS patients. METHODS: This was a cross-sectional study of 150 self-identified AA and 150 white patients with MS who underwent magnetic resonance imaging scan of brain and CSF sampling. Intrathecal IgG synthesis was quantified as IgG index. The Spearman test was used for univariate correlation analysis, followed by generalized linear model (GLM) to assess the effect of race on the correlation between IgG index and GM volume. RESULTS: The GM volume was inversely related to the IgG index for the entire group (rho = -.57, P < .0004). The AA group showed a stronger correlation (rho = -.893, P < .00004), as compared to whites (rho = -.019, P = .85), between GM and IgG index. Furthermore, GLM analysis showed a significant effect of race on the relation between IgG index and GM volume (P < .0005). CONCLUSIONS: AA patients with MS have lower GM volume and a stronger inverse correlation between GM volume and CSF IgG index, compared to the whites. These findings suggest a potentially prominent role of humoral immunity in mediating tissue injury in AA patients with MS.

The Relationship Between Brain MR Spectroscopy and Disability in Multiple Sclerosis: 20-Year Data from the U.S. Glatiramer Acetate Extension Study.

BACKGROUND AND PURPOSE: Conventional MRI techniques do not necessarily provide information about multiple sclerosis (MS) disease pathology or progression. Nonconventional MRI techniques, including proton magnetic resonance spectroscopy (1 H-MRS), are increasingly used to improve the qualitative and quantitative specificity of MR images. This study explores potential correlations between MRI measures of disease and disability progression as measured by the Expanded Disability Status Scale (EDSS), Functional Systems (FS), and ambulation index scores in a unique cohort of MS patients treated with glatiramer acetate that has been closely monitored for over 20 years. METHODS: This was a multicenter, open-label, cross-sectional MRI substudy among participants in the GA-9004 open-label extension of the 36-month, double-blind GA-9001 study, timed to coincide with the prospectively planned 20-year clinical exam. RESULTS: Of 64 patients who participated in the MRI substudy, results are presented for the 39 patients (61%) who had a 1 H-MRS assessment at 20 years of treatment. Both total N-acetylaspartate relative to total creatinine (tNAA/tCr) concentration ratio and T1 lesion volume were found to be robustly associated with disability levels with different statistical approaches. Gray matter (GM) volume was found to be a more consistent parameter than white matter (WM) volume for disability allocation. The elastic net algorithm showed a trade-off between WM and GM volumes for disability estimation when different disability definitions were used. CONCLUSIONS: Among patients with MS receiving long-term glatiramer acetate therapy, consistent effects on disability levels indicated by EDSS and pyramidal FS score thresholds were found for tNAA/tCr concentration ratio and T1 lesion volume.

Design of an Intelligent Nursing Clinical Pathway and Nursing Order Support System for Traditional Chinese Medicine.

With an in-depth analysis of nursing work in 14 hospitals over a period of two years, one unique total nursing information system framework was established where the nursing clinical pathways are used as the main frame and the nursing orders as the nodes on the frame. We used the nursing order concept with the principles of nursing process. A closed-loop management model composed of the nursing orders was set up to solve nursing problems. Based on the principles of traditional Chinese medicine, we further designed an intelligent support module to automatically deduct clinical nursing pathways to promote standardized management and improve the quality of nursing care. The system has successfully been implemented in some facilities since 2015.

Characterizing retinal structure injury in African-Americans with multiple sclerosis.

To examine retinal structure injury in African-Americans (AA) with Multiple Sclerosis (MS) compared to Caucasians (CA) with MS, we used spectral domain optical-coherence tomography (OCT) in this cross sectional study. The peripapillary retinal nerve fiber layer (pRNFL) and macular volume of 234 MS patients (149 CA; 85 AA) and 74 healthy controls (60 CA; 17 AA) were measured. Intra-retinal segmentation was performed to obtain retinal nerve fiber (RNFL), ganglion cell (GCL), inner plexiform (IPL), inner nuclear (INL), outer plexiform (OPL), outer nuclear (ONL), retinal pigment epithelium (RPE), and photoreceptor (PR) layer volumes. Study was approved by IRB, and informed consent obtained from all participants. We found that pRNFL was thicker in AA v. CA healthy controls (100.9 vs 97.00µm, p=0.004). Compared to HC, MS patients demonstrated thinner pRNFL (p<0.0001), and lower TMV (p<0.001), macular RNFL (p<0.0001), GCL (p<0.0001), and IPL (p<0.0001). AAMS patients had thinner pRNFL (87.2 vs 90.0µm, and lower TMV (8.2 vs 8.4mm(3), p=0.0001), RNFL (0.73 vs 0.79mm(3), p=0.0001), and GCL (0.94 vs 0.98mm(3), p=0.007) than CAMS patients. Sub-analysis of patients without history of AON showed thinner pRNFL (88.9 vs 93.1µm) and TMV (8.2 vs. 8.5mm(3), p<0.0001) in AAMS compared to CAMS patients. In conclusion, this cross-sectional study provides evidence supporting greater retinal structure injury in AAMS compared to CAMS patients, irrespective of history of AON. Our findings are consistent with other studies demonstrating a more severe CNS tissue injury in AAMS patients.